The long-term objective of this research is to develop a technique for the noninvasive detection of early lung carcinoma using volatile organic constituents in expired air. Preliminary results published by our group have identified several volatile organic compounds that appear to be associated with lung cancer. The primary objective of the 3-year study is to extend these observations and to explore the diagnostic potential of such compounds using statistical approaches. A study population of 325 subjects will be screened over a 3-year period. These subjects will include 100 lung cancer patients and 75 subjects in each of 3 propensity score matched control groups (normal smoking controls, noncancer lung diseases, and nonpulmonary cancers). Four samples (2 fasting and 2 two-hr postprandial) will be collected from each subject. Two samples will be analyzed immediately and the 2 duplicate samples will be used for backup and quality assurance audits. The collected expired air will be collected, processed, and analyzed by techniques previously developed in this laboratory. An estimation and a validation phase will be conducted. In the estimation phase, variables (peaks) will be screened both individually and in combination for statistical significance. In the validation phase, those variables that were statistically significant in the estimation phase will be reexamined in a new sample of patients to determine if this previous significance was due to chance. If a variable (i.e., a GC peak representing a compound) or linear combination of variables is significant in both the estimation and validation phases, we will conclude that it is significantly related to the presence of lung cancer. We anticipate that the results of this study will advance preliminary data which will permit the early detection of lung cancer in a smoking population and ultimately result in the development of an inexpensive, routine, noninvasive laboratory procedure. (4)